Oncogenic protein kinases such as cMet represent a class of biologically important targets for cancer intervention. cMet, a well characterized receptor tyrosine kinase encoded by the MET proto-oncogene, is the cell surface receptor for hepatocyte growth factor (HGF; Gherardi E, Birchmeier W, Birchmeier C et al. Targeting MET in cancer: rationale and progress. Nat Rev Can. 2012; 12:89-103). cMet overexpression occurs in approximately 30%-50% of solid tumors including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and advanced gastroesophageal cancer (AGEC) (Spigel D R, Ervin T J, Ramlau R A, et al. Randomized Phase II trial of onartuzumab in combination with erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2013; 31(32):41054114; Resnick M B, Routhier J, Konkin T et al. Epidermal growth factor receptor, cMET, B-catenin, and p53 expression as prognostic indicators in stage II colon cancer: a tissue microarray study. Clin Can Res. 2004; 10:3069-3075; Lee H E, Kim M A, Lee H S, et al. MET in gastric carcinomas: comparison between protein express and gene copy number and impact on outcome. Br J Can. 2012; 107(2):325-333).
Overexpression of cMet has been associated with poor patient outcome. Thus, there remains a need for cancer therapeutics that target solid tumor cancers characterized by overexpression of cMet.